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Overview DNA Repair Mechanisms Prereplication Repair Overview Chapter 10 continued… • Mutation changes one allelic form to another and is the ultimate source of genetic variation. • Mutational variation underlies the study of genetics. • Mutations are produced by mutagens or occur Gene Mutation: Origins and spontaneously. Repair Processes • Point mutations include single base-pair substitutions, additions or deletions. GAATTC → GTATTC • Some types of mutation can be repaired. A → a • Specialized forms of mutation include expansion of trinucleotide repeats and insertion of transposable elements. Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company DNA repair mechanisms • Direct reversal of damage – photodimer repair by photolyase • regenerates pyrimidines in presence of light – alkyltransferase • remove alkyl groups added by mutagen – neither system completely effective • Homology-dependent repair systems – take advantage of complementary nature of DNA molecule • excision repair, repairs damage before replication • postreplication repair, repairs during or after S phase – may have played role in evolution of sex Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Prereplication repair Excision • Nucleotide excision-repair system Repair in – recognizes abnormal base(s) through distortion of helix E. coli, red – excises lesion and flanking bases Indicates Break • 12-13 nucleotides in prokaryotes Points, orange • 27-29 nucleotides in eukaryotes Indicates T-T – uses complement to synthesize replacement strand dimer • Base-excision repair – DNA glycosylases remove base – repaired by AP site-specific endonuclease pathway which repairs spontaneous loss of purine or pyrimidine Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company 1 Postreplication repair • Mismatch repair system – recognizes mismatched base pairs – determines which base is incorrect one • distinguishes old template strand from new strand by delayed methylation that normally occurs • methyladenine on old strand in GATC sequence – excision of base followed by templated repair • Recombinational repair – recA gene product – gap repaired by DNA cut from sister molecule Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Mobile elements and mutation • Also known as transposable elements • Encode transposase enzyme • Types of prokaryotic mobile elements – insertion sequence (IS) • plasmids or chromosome • may move from one location to another – bacterial transposons (TN) • include genes conferring drug resistance (R factors) • ends consist of identical IS sequences in opposite orientation Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company 2 IS and the genes they surround are called transposons (TN) or mobile elements, and vary in size and number IS10 bounds the region containing genes for tetR - and like other transposable elements, can jump from a plasmid to a chromosome, or to another plasmid Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Mechanisms of transposition • Replicative transposition – copy of transposon left behind – new copy inserted elsewhere in genome – mediated by transposon-specific transposase enzyme • Conservative transposition – excise from location and integrate elsewhere – mediate by transposon-specific transposase – transposon often flanked by duplicate repeat sequence generated by insertion Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company The copy number of a Tn can grow, depending on the mechanism of transposition Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company 3 Eukaryotic mobile elements • Historically, mobile elements were discovered in eukaryotes by genetic analysis – Barbara McClintock working with maize – Ac (activator) element • Mobile elements are common in eukaryotes Insertion sometimes leads to duplication of target sequences – utilize transposase, as in prokaryotes – may cause mutation by insertion into gene • Several categories – based on mode of replication and transposition – also based on types of extra genes present Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company General life cycle of a retrovirus: ssRNA>>dsDNA>>ssRNA Retroviral-like mobile elements • Transpose through RNA intermediate – e.g., copia in Drosophila • 4-9 kb in length • long terminal repeat (LTR) • reverse transcriptase copies RNA into DNA – may or may not have LTR • In mammals, includes – LINES (long) • functional elements – SINES (short) • nonfunctional elements Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Gag: group specific antigen, proteins of the viral core; Pol: reverse transcriptase; env: envelope proteins for fusion; Int: a transmembrane protein, probable receptor and growth factor Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company 4 Chapter 11 Chromosome Mutations Variation in chromosome number and structure Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company Overview • Multiples of complete sets of chromosomes are called polyploidy. – Even numbers are usually fertile. – Odd numbers are usually sterile. • Aneuploidy refers to the gain or loss of single chromosomes, usually in meiosis. • Chromosome aberrations include translocations, inversion, deletion, duplication. – Each has characteristic meiotic pairing. – Crossing-over may result in abnormal gametes, reduced fertility and unmasking of deleterious recessive alleles. – Duplication can also provide material for evolutionary divergence. Chapter 10: Gene mutation © 2002 by W. H. Freeman and Company 5.
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